Methods for identifying compounds for regulating muscle mass of function using amylin receptors
AssigneeThe Procter & Gamble Company
InventorsRobert Joseph Isfort, Russell James Sheldon
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Abstract
Screening methods for identifying compounds that bind to or activate amylin receptors (AR) and regulate or potentially regulate skeletal muscle mass or function in vivo. Also disclosed are screening methods for identifying compounds that prolong or augment the activation of ARs or of AR signal transduction pathways, increase AR or increase amylin expression are provided. Pharmaceutical compositions comprising AR agonists, antibodies to AR and methods for increasing skeletal muscle mass or function or for the treatment of skeletal muscle atrophy using AR as the target for intervention and methods for treatment of muscular dystrophies are described.
Claims22
A method for identifying candidate compounds for regulating skeletal muscle mass or function, comprising:
- a. contacting a test compound with an amylin receptor;
- b. determining whether the test compound binds to the amylin receptor;
- and
- c. identifying those test compounds that bind the amylin receptor as candidate compounds for regulating skeletal muscle mass or function.
A method for identifying candidate compounds for regulating skeletal muscle mass or function, comprising:
- a. contacting a test compound with a cell expressing a functional amylin receptor;
- b. determining whether the test compound activates the amylin receptor;
- and
- c. identifying those test compounds which activate the amylin receptor as candidate compounds for regulating skeletal muscle mass or function.
A method for identifying candidate compounds for regulating skeletal muscle mass or function comprising:
- a. contacting a test compound with a cell expressing a functional amylin receptor, and determining the level of activation of the amylin receptor;
- b. contacting the test compound with a cell expressing a functional calcitonin receptor, and determining the level of activation of the calcitonin receptor;
- c. comparing the level of amylin receptor activation in the cell expressing a functional amylin receptor to the level of calcitonin receptor activation in the cell expressing calcitonin receptor;
- and
- d. identifying those test compounds that show selectivity for amylin receptor as candidate compounds for regulating skeletal muscle mass or function.
A method for identifying candidate compounds for regulating skeletal muscle mass or function by identifying compounds that prolong or augment the agonist-induced activation of an amylin receptor or of an amylin receptor signal transduction pathway, comprising;
- a. contacting a test compound with a first cell population which expresses a functional amylin receptor;
- b. treating a second cell population with an amylin receptor agonist for a sufficient time and at a sufficient concentration to cause desensitization of the amylin receptor;
- further treating the second cell population with the test compound;
- c. determining the level of activation of the amylin receptor in the first and second cell population;
- and
- d. identifying those test compounds that prolong or augment the activation of an amylin receptor or of an amylin receptor signal transduction pathway as candidate compounds for regulating skeletal muscle mass or function.
A method for identifying candidate therapeutic compounds from a group of one or more candidate compounds which have been previously determined to bind, or activate an amylin receptor;
- or prolong, or augment the activation of an amylin receptor or of an amylin receptor signal transduction pathway comprising:
- a. administering the candidate compound, or the candidate compound in conjunction with an amylin receptor agonist, to a non-human animal;
- and
- b. determining whether the candidate compound regulates skeletal muscle mass or function in the treated animal.
A method for identifying candidate compounds for regulating skeletal muscle mass or function by identifying compounds that increase expression of amylin or amylin receptor, comprising:
- a. contacting a test compound with a cell or cell lysate containing a reporter gene operatively associated with calcitonin receptor gene regulatory element, receptor activity modifying protein gene regulatory element, or an amylin gene regulatory element;
- b. detecting expression of the reporter gene;
- and
- c. identifying those test compounds that increase expression of the reporter gene as candidate compounds for regulating skeletal muscle mass or function.
A method for increasing skeletal muscle mass or function in a subject in which such an increase is desirable, comprising:
- a. identifying a subject in which an increase in muscle mass or function is desirable;
- and
- b. administering to the subject a safe and effective amount of a compound selected from the group consisting of an amylin receptor agonist, a compound that augments or prolongs amylin receptor or amylin receptor signal transduction pathway activation, an expression vector encoding a functional amylin receptor, an expression vector encoding a constitutively active amylin receptor, an expression vector encoding amylin and a compound that increases expression of an amylin receptor or amylin.
A pharmaceutical composition, comprising:
- a. a safe and effective amount of an amylin receptor agonist;
- and
- b. a pharmaceutically-acceptable carrier.
Dependencies are inferred from the claim text.